DNA Shape Dominates Sequence Affinity in Nucleosome Formation
DNA Shape Dominates Sequence Affinity in Nucleosome Formation
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DOI：
10.1103/physrevlett.113.168101
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发表时间：
2014-10-14
影响因子：
8.6
通讯作者：
de Pablo, Juan J.
中科院分区：
文献类型：
--
作者：
Freeman, Gordon S.;Lequieu, Joshua P.;de Pablo, Juan J.
核小体提供了真核基因组中压缩的基本单位，而决定它们在 DNA 序列中特定位置的位置的机制对于遗传学至关重要。在这封信中，我们利用 DNA 和蛋白质的分子模型来阐明核小体定位的各个方面。特别是，我们展示了 DNA 的组蛋白亲和力如何以其序列依赖性形状进行编码，包括与理想的直 B-DNA 形式的细微偏差和小沟宽度的局部变化。通过对核小体复合物自由能的高精度模拟，我们还证明，根据 DNA 的固有曲率，组蛋白结合可能由弯曲相互作用或静电相互作用主导。更一般地说，这里提出的结果解释了序列（表现为 DNA 分子的形状）如何在核小体定位问题中主导分子识别。
Nucleosomes provide the basic unit of compaction in eukaryotic genomes, and the mechanisms that dictate their position at specific locations along a DNA sequence are of central importance to genetics. In this Letter, we employ molecular models of DNA and proteins to elucidate various aspects of nucleosome positioning. In particular, we show how DNA's histone affinity is encoded in its sequence-dependent shape, including subtle deviations from the ideal straight B-DNA form and local variations of minor groove width. By relying on high-precision simulations of the free energy of nucleosome complexes, we also demonstrate that, depending on DNA's intrinsic curvature, histone binding can be dominated by bending interactions or electrostatic interactions. More generally, the results presented here explain how sequence, manifested as the shape of the DNA molecule, dominates molecular recognition in the problem of nucleosome positioning.